A mechanism that seems to slow down – and could prevent – the natural ageing of immune cells has been identified in what scientists said was an unexpected discovery.
An international team, led by researchers at University College London, believe harnessing the mechanism could extend the life of the immune system, which would allow people to have healthier and longer lives.
The findings, published in *Nature Cell Biology*, researchers say the discovery in-vitro and validated in mice was “unexpected”.
Lead author, Dr Alessio Lanna, honorary professor at UCL Division of Medicine, said: “Immune cells are on constant high-alert, always ready to fight pathogens. To be effective they also must persist for decades in the body – but the strategies employed to execute this life-long protection are largely unknown.
“In this research, we sought to find out what mechanisms exist to confer longevity to immune system cells, known as T cells, at the initiation of the immune response against an antigen – a foreign substance recognised by the immune-surveillance mechanisms of defence of the body.”
Each of the chromosomes contains a telomere, a specific DNA sequence that is repeated thousands of times. The sequence has two purposes: to protect the coding regions of the chromosomes and prevent them from being damaged, and to act as an ageing clock that controls the number of replications a cell can make.
In T cells and most other cells, the telomeres become shorter with each subsequent cell division and once they reach a critically short length, the cell enters senescence.
This telomere attrition has been described as one of the hallmarks of ageing and leads to the onset of chronic infections, cancer and death.
In the study, researchers initiated an immune response of T-lymphocytes against a microbe in vitro.
They observed a telomere transfer reaction between two types of white blood cells, in extracellular vesicles. An antigen presenting cell (APC), consisting of B cells, dendritic cells or macrophages, functioned as a telomere donor to the T lymphocyte.
Once the telomeres were transferred, the recipient T cell became long-lived and possessed memory and stem cell attributes. This allowed the T cell to protect a host against a lethal infection in the long term.
The telomere transfer reaction extended certain telomeres about 30 times more than extension exerted by telomerase.
Prof Lanna said: “The telomere transfer reaction between immune cells adds to the Nobel-prize winning discovery of telomerase and shows that cells are capable of exchanging telomeres as a way to regulate chromosome length before telomerase action begins. It is possible that ageing may be slowed down or cured simply by transferring telomeres.”
The research team went on to establish that telomere extracellular vesicles can be purified from the blood, and when they are added to T cells, present anti-ageing activities in immune systems from both humans and mice.
They found the purified extracellular vesicle preparations can be administered alone or combined with a vaccine, which extended durative immune protections.
The telomere donor transfer reaction can also be boosted directly in cells.
“Telomere biology has been studied for more than 40 years. For decades, a single enzyme, telomerase, has been credited as the sole mechanism responsible for telomere elongation and maintenance in cells,” said Prof Lanna.
“Our results illuminate how a different mechanism that does not require telomerase to extend telomeres and act when telomerase is still inactive in the cell.”
Lanna A, Vaz, D’Ambra et al. Intercellular telomere transfer rescues T cells from senescence and promotes long-term immunological memory. *Nature Cell Biology* 15 September 2022
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